Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/64—Fluorescence; Phosphorescence
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
  • G01N21/6454—Individual samples arranged in a regular 2D-array, e.g. multiwell plates using an integrated detector array
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/64—Fluorescence; Phosphorescence
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
  • G01N21/03—Cuvette constructions
  • G01N21/0303—Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
  • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
  • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2201/00—Features of devices classified in G01N21/00
  • G01N2201/04—Batch operation; multisample devices
  • G01N2201/0407—Batch operation; multisample devices with multiple optical units, e.g. one per sample
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2201/00—Features of devices classified in G01N21/00
  • G01N2201/06—Illumination; Optics
  • G01N2201/064—Stray light conditioning
  • G01N2201/0642—Light traps; baffles

Definitions

• the invention relates to a measuring device for luminescence measurement.
• Such a measuring device is known, for example, from US Pat. No. 5,827,748 and makes it possible, for example, to measure photoluminescence in the case of samples.
• the samples to be measured are in this case on a serving as a sample carrier transparent
• Substrate arranged and optically excited by a lighting unit to cause photoluminescence.
• a lighting unit to cause photoluminescence.
• a lens array serving as a sample carrier
• an optical filter and, finally, a light sensor which measures the luminescence radiation emanating from the sample are located behind one another in the beam path of the luminescence radiation.
• a disadvantage of this known measuring device is the lacking possibility of extensive miniaturization, since the lens array is designed as a GRIN lens array (GRIN: graded index of refraction), which generally has a much greater thickness (typically more than 5 mm) as the height of a microlens in the microlens array (typically a few ⁇ ).
• GRIN graded index of refraction
• the invention thus comprises the general technical teaching of replacing the GRIN lens array by a microlens array in the conventional measuring device described above, which is considerably thinner and therefore makes miniaturization possible.
• the invention provides that a shadow mask with numerous holes is arranged in the beam path of the luminescence radiation between the sample carrier and the microlens array, wherein the individual microlenses and the holes are associated with one another and have matching axes.
• this shadow mask does not increase the thickness of the system because the object plane of the microlens array is above the shadow mask.
• the holes in the shadow mask are preferably arranged in the form of a grid, just as the individual microlenses in the microlens array are preferably arranged in the form of a grid.
• the individual holes in the shadow mask and the microlenses in the microlens array are arranged arbitrarily, ie without a grid-shaped or other geometric Order. All that matters is that the optical axes of the holes of the shadow mask on the one hand and the individual microlenses of the microlens array on the other hand coincide.
• microlens arrays used according to the invention are known per se from the prior art and therefore need not be described in detail. It should merely be mentioned at this point that the microlens array according to the invention is very thin and has a thickness which is preferably less than 2 mm, 1 mm, 500 ⁇ m, 200 ⁇ m, 100 ⁇ m or even less than 50 pm. As a result, the microlens array enables miniaturization of the measuring device according to the invention. Since the meter has only small and light elements, it can be portable or even be designed as a hand-held device.
• an optical filter eg an interference filter
• the optical filter substantially reflects or absorbs an excitation radiation for the photoluminescent sample, while the optical filter Luminescence radiation emanating from the sample substantially passes.
• the optical filter is thus intended to prevent the ⁇ for the optical excitation of the photoluminescent sample ⁇ nende excitation radiation is misdiagnosed by the light sensor, as this leads to a falsification of the luminescence would lead. If the excitation radiation and the resulting luminescence radiation are in different wavelength ranges, this can be achieved by the optical filter having a corresponding spectral characteristic which blocks the excitation radiation, whereas the luminescence radiation is transmitted.
• a further shadow mask with numerous grid-shaped holes can also be arranged.
• This further shadow mask coincides with the first shadow mask, preferably with regard to the arrangement of the holes, so that the holes of the two shadow masks lie one above the other in coincidence.
• the two shadow masks may differ in their thickness and in the diameter of their holes.
• This additional shadow mask has the function of further minimizing the overlapping of the measuring regions and reducing the background intensity.
• a further microlens array with numerous microlenses to be arranged in the beam path of the luminescence radiation emanating from the sample between the sample carrier and the light sensor.
• the optical axes of the individual Mikrolin ⁇ sen this further microlens array preferably coincide with the optical axes of the other microlens array, and the holes of the shadow mask.
• a third shadow mask with numerous holes is arranged in the beam path of the luminescence radiation emanating from the sample between the sample carrier and the light sensor, the holes preferably being distributed in grid form are.
• the holes of the third shadow mask coincide with the holes of the other shadow masks and the microlenses of the microlens arrays.
• the first shadow mask, the first microlens array and the optical filter are arranged one behind the other in the beam path of the luminescence radiation emanating from the sample between the sample carrier and the light sensor.
• the first shadow mask, the first micro-lens array, the second shadow mask, the second microlens array, the third shadow mask and the optical filter are located one behind the other in the beam path of the luminescence radiation emanating from the sample.
• the invention is not limited to the three variants described above, but in principle can also be implemented with other sequences of components in the beam path of the luminescence radiation emanating from the sample, whereby further components can also be added.
• the two microlens arrays preferably have a common image and object plane lying in the plane of the third shadow mask, ie the second shadow mask following in the beam path.
• This quasi-confocal adjustment of the microlenses of the two microlens arrays, together with the thin hole mask in between, enables the measurement of only the fluorescence signals coming from the image and object plane of the microlenses of the first microlens array.
• this plane coincides with the surface of the sample carrier (eg waveguide) on which the fluorescent material lies.
• the shadow masks and the microlens arrays preferably have matching grid dimensions. This means that the holes or microlenses are arranged in a grid-shaped manner at a predetermined distance from each other and at predetermined positions.
• the holes in the different shadow masks have a different size, as already briefly mentioned above.
• the different shadow masks can also have different thicknesses, as has already been mentioned above.
• the holes in the individual shadow masks can be made with a transparent filling material and in the case of the third shadow mask this transparent filling material should preferably have the same refractive index as the material of the microlenses of the microlens arrays.
• the filling of the holes can be done either with one, several or all shadow masks.
• the optical axes of the individual microlenses of the microlens arrays preferably each extend coaxially to the holes of the shadow masks adjacent in the beam path.
• the individual shadow masks preferably have a thickness of less than 3 mm, 1 mm or 0.5 mm in order to allow miniaturization of the measuring device according to the invention.
• the microlens arrays, the optical filter and the light sensor can be glued together, for example by means of an optical fine cement (eg Norland liquid), whose refractive index is preferably uniform with the material refractive index of the microlens arrays, which makes it practical save at least one optical interface.
• an optical fine cement eg Norland liquid
• the optical filter is also possible for the optical filter to be vapor-deposited as a layer on at least one surface of a microlens array of the light sensor.
• the sample carrier used is a waveguide in which the excitation radiation can propagate to excite the photoluminescent sample.
• the measuring device according to the invention therefore preferably also comprises a lighting unit to generate the excitation radiation to excite the photo-luminescent sample, wherein the excitation radiation is coupled from the lighting unit in the waves ⁇ conductor.
• the waveguide is substantially planar and has a waveguide. Edge, wherein the excitation radiation of the illumination unit is coupled through the waveguide edge of the waveguide.
• the coupling of the excitation radiation into the waveguide can also take place in a planar waveguide in a different manner, for example by means of gratings or prisms.
• the illumination unit has a specific focal plane, wherein the waveguide edge of the waveguide lies in the focal plane of the illumination unit.
• the illumination unit generates a light line that runs along the waveguide edge, so that the excitation radiation is coupled into the waveguide even over the entire length of the waveguide edge.
• a diaphragm is arranged in the beam path of the excitation radiation in front of the waveguide edge, which passes through the excitation radiation to the waveguide edge, while the diaphragm otherwise shields the excitation radiation. This is advantageous because it reduces the risk of misdetection of the excitation radiation by the light sensor.
• the illumination unit initially has a light source in order to generate the excitation radiation for exciting the photoluminescent sample.
• the light source is preferably a laser diode, but other types of light sources can be used within the scope of the invention.
• the illumination unit preferably has an optical filter which only passes through a narrow-band wavelength spectrum, the optical filter being arranged in the beam path of the light source.
• the spectral filter characteristic of the optical filter is designed, for example, such that the wavelengths required for the optical excitation of the photoluminescence are transmitted, whereas the wavelength spectrum of the luminescence radiation is blocked. This is advantageous because the risk of misdetection of the excitation radiation by the light sensor is lower due to this wavelength separation.
• the optical filter can be an interference filter, but the invention can also be implemented with other types of filters.
• the illumination unit according to the invention preferably comprises a line lens which expands the light beam emanating from the light source to a line of light to illuminate the waveguide edge over most of its length.
• the line lens is preferably arranged in the beam path of the light source behind the optical filter.
• the lighting unit preferably includes a cylindrical lens for reducing the divergence of the light emitted from the illumination unit Be ⁇ excitation radiation, wherein the cylindrical lens in the beam path of the light source is preferably disposed behind the line lens.
• the sample carrier is preferably designed as a waveguide. With regard to the arrangement of the sample on the waveguide, there are various possibilities. Thus, the sample and the light sensor may be disposed on opposite sides of the waveguide. However, in principle there is also the possibility that the sample and the light sensor are arranged on the same side of the waveguide, which is less preferred. Furthermore, there is also the possibility that the sample is arranged in the waveguide itself.
• the waveguide is preferably transparent at least for the serving for exciting the photoluminescent sample excitation radiation, preferably completely or to ⁇ least in one layer.
• the waveguide in the transparent layer preferably has a refractive index which is greater than the refractive index of the environment, in particular on the side of the sample and on the side of the light sensor.
• the light sensor preferably has a planar detector surface which is arranged parallel to the planar sample carrier (eg waveguide).
• the light sensor can be, for example, a CCD sensor (CCD: Charge-Coupled Device) or a CMOS sensor (CMOS: Complementary Metal Oxide Semiconductor), but in principle the invention can also be implemented with other types of light sensors.
• CCD Charge-Coupled Device
• CMOS Complementary Metal Oxide Semiconductor
• FIG. 1B shows a simplified exploded view of the readout system according to FIG. 1A
• FIG. 2A shows a modification of the readout system from FIG. 1A with a plurality of microlens arrays and a plurality of shadow masks
• FIG. 2B shows a simplified exploded view of the read-out system from FIG. 2A
• Figure 3A is a modification of Figure 2A
• Figure 3B is a modification of Figure 2B
• Figure 4 is an exploded view of an inventive
• Measuring device according to another embodiment.
• Figures 1A and 1B show a first embodiment of a measuring device according to the invention for the measurement of photoluminescence, wherein the measuring device consists essentially of the lighting unit 1 and a readout system 2.
• the illumination unit 1 has as a light source a Laserdi ⁇ ode 3, which emits a light beam 4 for Photolumineszenzan ⁇ movement.
• an interference filter 5 is arranged, which passes only a narrow wavelength interval of the light beam 4.
• the spectral characteristic of the interference filter 5 is here tuned so that the interference filter 5 transmits the required for photoluminescence excitation radiation, whereas the interference filter 5 blocks the resulting luminescence. This spectral separation of the excitation radiation from the luminescence radiation offers the possibility of preventing crosstalk of the laser diode 3 onto the readout system 2, as a result of which the risk of misdetection of the excitation radiation is lower.
• a line lens 6 is arranged in the beam path of the light beam 4 behind the interference filter 5, which fanning the light beam 4 at right angles to the plane and generates a light line, which is advantageous for coupling the excitation radiation in the readout system 2, as will be described in detail.
• the illumination unit 1 also comprises a cylindrical lens 7 which is arranged behind the line lens in the beam path of the light beam 4, the cylindrical lens 7 minimizing the divergence of the light beam 4.
• the readout system 2 has a planar waveguide 8 as a sample carrier, wherein the waveguide 8 can always be positioned at the same position on a sensor surface of the readout system 2 with the aid of a fixing frame (not illustrated here).
• the samples 9 to be measured On the upper surface of the waveguide 8 in the drawing are the samples 9 to be measured, which are photoluminescent samples which are excited by the excitation radiation from the illumination unit 1 for photoluminescence.
• the excitation radiation is coupled into the readout system 2 via a waveguide edge 10 of the waveguide 8.
• the light line generated by the illumination unit 1 coincides here with the waveguide edge 10, which enables an efficient coupling of the excitation radiation in the waveguide 8.
• the waveguide 8 is thus completely or at least transparent in a layer for the wavelength of the originating from the Be ⁇ illumination unit 1 excitation radiation so that the excitation radiation to the sample 9 can get.
• the refractive index of the Wellenlei- ters 8 in the transparent region is larger than the refractive index of the ⁇ environment. This ensures that the excitation radiation emanating from the illumination unit 1 can propagate within the waveguide 8 and excite the photoluminescent samples 9.
• the photo- luminescent samples 9 is excited ⁇ on the surface of the waveguide 8 by the evanescent field of the propagating light modes.
• lenleiters 8 is a shadow mask 11 having a number of grid-like arranged holes 12, a microlens array 13 having a number of grid-like arranged microlenses 14, an opti ⁇ ULTRASONIC filter 15 and finally a CCD sensor 16 to the read-out system 2 below the WEL.
• the shadow mask 11 and the microlens array 13 in this case have matching grid dimensions, so that the optical axes of the individual microlenses 14 of the microlens array 13 coincide with the holes 12 of the shadow mask 11.
• the shadow mask 11 serves as incident direction filter, which prevents the overlapping of different measuring regions.
• the shadow mask 11 also serves as a spacer between the surface of the waveguide 8 and the microlens array 13.
• the optical filter 15 is preferably an interference filter that reflects or blocks the wavelength of the excitation radiation originating from the illumination unit 1, whereas the optical filter 15 transmits the wavelength of the luminescence radiation originating from the samples 9. In this way, the optical filter 15 prevents crosstalk of the excitation radiation originating from the illumination unit 1 to the CCD sensor 16.
• the CCD sensor 16 measures the originating from the sample 9 Lu ⁇ mineszenzstrahlung under each grid point independently and forwards measured values corresponding with its readout electronics further to a computer, where takes place later image processing.
• the readout system 2 thus enables the photoluminescence measurement at the point where the fluorescence signal of the sample 9 passes through the waveguide 8 and then through the corresponding hole 12 of the shadow mask 11 and with the help of the microlens array 13 on the surface of the CCD Sen ⁇ sors 16 is shown.
• FIGS 1A and 1B show a modification of the embodiment according to FIGS 1A and 1B, reference is therefore made to avoid repetition of the foregoing description, and the same for corresponding details reference sign ⁇ be used.
• a special feature of this embodiment is that in the readout system 2 in the beam path of the luminescence between the optical filter 15 and the CCD sensor 16, a further shadow mask 17 is arranged with numerous grid-shaped holes 18.
• the shadow mask 17 coincides with the shadow mask 11 with regard to the grid dimension of the holes 18.
• the two shadow masks 11, 17 differ in terms of their thickness and in terms of the diameter of the holes 12, 18.
• the additional shadow mask 17 has the task of further minimizing the overlapping of the measuring regions and reducing the background intensity.
• FIGS. 3A and 3B show a further modification of the embodiment according to FIGS. 1A and 1B or 2A and 2B, so that reference is made to the above description to avoid repetition, the same reference numbers being used for corresponding details.
• a special feature of this embodiment is that the second shadow mask 17 is arranged in the beam path of the luminescence radiation ⁇ front of the optical filter 15 and behind the micro-lens array. 13
• the read-out system 2 in this exemplary embodiment has a further microlens array 19 with numerous microlenses 20 and a further shadow mask 21 with numerous holes 22, the microlens arrays 13, 19 and the shadow masks 11, 17, 21 having matching grid dimensions, such that the holes 12, 18, 22 of the shadow masks 11, 17, 21 coincide with the optical axes of the microlenses 14, 20 of the microlens arrays 13, 19.
• the two microlens arrays 13, 19 hereby have common image and object planes that lie in the plane of the shadow mask 21.
• the holes 22 of the shadow mask 21 are filled with a transparent filling material, wherein the refractive index of the filling material coincides with the refractive index of the material of the microlens arrays 13, 19.
• FIG. 4 shows a further exemplary embodiment of a measuring device according to the invention for luminescence measurement.
• This exemplary embodiment largely corresponds to the exemplary embodiments described above, so that reference is made to the above description to avoid repetition, the same reference numerals being used for corresponding details.
• this drawing also shows a cover 23 and a spacer 24th
• a measuring device advantageously allow miniaturization, which allows use in so-called point-of-care diagnostics.
• the measuring device according to the invention can also be used in mobile laboratories, for example in ambulances.
• the invention is not limited to the preferred embodiments described above. Rather, a multiplicity of variants and modifications is possible, which likewise make use of the concept of the invention and therefore fall within the scope of protection.
• the invention also claims protection for the subject matter and the features of the subclaims independently of the claims referred to.

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• Health & Medical Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Physics & Mathematics (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

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• 2012
  • 2012-09-14 DE DE102012018303.8A patent/DE102012018303A1/de not_active Withdrawn
• 2013
  • 2013-09-11 EP EP13759987.4A patent/EP2895843A1/fr not_active Withdrawn
  • 2013-09-11 WO PCT/EP2013/002732 patent/WO2014040730A1/fr not_active Ceased

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